Non-halogenated naphthol compounds, antimicrobial compositions containing the same, and methods of using the same

ABSTRACT

An antimicrobial compound, composition containing such compound, and method of use of the same for reducing the presence of microorganism on a substrate or in a fluid environment comprising an antimicrobial effective carrier and one or more essential antimicrobial compounds including non-halogenated naphthol compounds.

[0001] This application claims the benefit of U.S. Provisional PatentApplication No. 60/256,787, filed on Dec. 20, 2000, the entirety ofwhich is hereby incorporated by reference as if fully set forth herein.

FIELD OF THE INVENTION

[0002] The present invention relates to antimicrobial compounds, andcompositions containing such compounds, and more particularly tonon-halogenated naphthol compounds exhibiting antimicrobial activity,antimicrobial compositions containing non-halogenated naphtholcompounds, and methods of using such compositions.

BACKGROUND OF THE INVENTION

[0003] Recently, attention has focused on personal hygiene in light ofmounting concerns about public health. There is a growing awareness ofvarious microorganisms and microbial pathogens such as yeast, fungi,bacteria, molds and viruses, that can cause disease upon access andentry into the body such as through the eyes, ears, nose, mouth andskin. These microbes are generally transmitted from a source (e.g. acontaminated surface) by the hands to a person's body. Thus, a number ofillnesses may easily be prevented by decontamination of the skin and thehands. In a related vein, the control of pathogenic or otherwiseundesirable microbes is also a concern in promoting good oral hygiene,where reducing populations of microorganisms on the teeth, gums andtongue has been shown useful in controlling dental plaque accumulation,gingivitis, oral malodor, and other oral maladies.

[0004] It has been shown that at least 18 percent of the population isafflicted with some form of a microbial infection of the dermis.Although such infections are more common in third world areas, there isalso a substantial incidence of the infections in developed areas wherea high level of personal hygiene exists. Studies have further shown thatthe factors that contribute to rising incidence of such infectionsinclude longer lifespans, emerging resistance of microbes toantibiotics, increased use of antineoplastic agents, and a growingpopulation of patients with some deterioration in their immune system.

[0005] Microbial infections and disease are caused by many types ofmicroorganisms. Most infections are typically the result of microbialinfection and/or the presence of microorganisms such as on the skin ofthe hand or foot, for example. Accordingly, it has been noted thateffective treatments of such infections should also include properpreventive measures, specifically, thorough sanitization of the skinincluding the hands and contact surfaces to prevent furthercontamination and/or transmission to other individuals.

[0006] Treatment of infection typically includes the application oftopical or systemic antibiotic/antifungal agents. Such therapies aredisadvantageous because they exhibit a limited rate of success, arecontraindicated and/or have undesirable drug interactions, produceelevated levels of toxicity, and/or are expensive. Additionally, thescientific and medical communities have moved away from the use of suchsystemic antimicrobial therapy for oral and general infection controldue to an increase in the number of resistant strains of pathogenicmicrobes.

[0007] Antimicrobial cleansing compositions for use on the hands, skin,and scalp have used a variety of antimicrobial ingredients includinganionic surface-active agent (e.g. sodium lauryl sulfate), coal tar,cationic antimicrobial agents such as chlorhexidine, and halogenatednonionic antimicrobial agents such as triclosan and hexachlorophene.

[0008] In addition to being present external to the body, microorganismsare also present in the oral cavity. Among undesirable microorganismsare Gram-positive and Gram-negative bacterial species associated withthe formation of dental plaque (a dense, enamel-adherent biofilmconsisting of microorganisms and their attendant extracellular matrix).Dental plaque is initially soft and removable by mechanical oralhygiene, but can undergo mineralization to form hard deposits of dentalcalculus. Although dental plaque may form on any part of the toothsurface, accumulation of plaque at the gingival margin is particularlyimplicated in the occurrence of gingivitis. Even with good oral hygiene,it has been shown that microorganisms (include those responsible forplaque formation) rapidly multiply and build up in the oral cavity, andmany individuals have difficulty in maintaining good plaque control withbrushing and flossing alone.

[0009] Specific areas, including periodontal and subgingival spaces, aswell as interpapillary spaces of the tongue and tonsils provide afavorable environment for harboring bacteria and other microbes. Quiteoften the use of dentifrices such as toothpaste, and/or toothbrushes,dental flosses, and cosmetic mouthrinses, is insufficient to control theundesirable microorganisms. The persistence of these microorganisms insuch environments greatly increases the risk of plaque and calculusbuild-up, which in turn presents a danger of gingival inflammation andmore advanced forms of periodontal disease. In addition, the productionof malodorous volatile compounds by accumulated populations of anaerobicmicroorganisms in dental plaque or on the tongue dorsum may lead toperceptible oral malodor.

[0010] Accordingly, it is highly desirable to include antimicrobial(antibacterial) agents in topical or oral compositions having biocidaland/or biostatic activity against a variety of microorganisms.Microorganisms of concern in hand and skin care include Gram-negativebacteria such as Escherichia coli and Pseudomonas aeruginosa, Grampositive bacteria such as Staphylococcus aureus and Propionibacteriumacnes, molds such as Aspergillus niger and Penicillium funiculosum,yeasts such as Candida albicans, Saccharomyces cerevisiae andPityrosporum ovale, dermatophytic fungi such as Trichophyton rubrum,microalgae such as Chlorella spp. and Spyrogyra spp., and viruses suchas Herpes virus and Picornavirus. Microorganisms of concern in dentalplaque, gingivitis, malodor and other oral maladies in the oral cavityinclude Fusobacterium nucleatum, Prevotella intermedia, Actinomycesviscosus, Streptococcus sanguis, Streptococcus mutans, and Candidaalbicans.

[0011] One type of oral composition used as a standard in oral hygieneis mouthrinse. However, many mouthrinses have only been effective inmasking halitosis. These include mouthrinses which comprise quaternaryamines (e.g., combinations of ethanol and domiphen bromide and/orcetylpyridinium chloride) or mixtures of orally acceptablesurface-active agents or surfactants. Several mouthrinses that have beenmarketed for the reduction of plaque and gingivitis generally rely oncationic agents such as chlorhexidine digluconate, metallic fluoridesalts such as stannous fluoride, antimicrobial essential oils (e.g.,thymol, eucalyptol, ethanol, menthol and methyl salicylate), and/orwater-insoluble phenolic agents such as triclosan.

[0012] The cationic antimicrobial materials such as chlorhexidine,benzethonium chloride, and cetyl pyridinium chloride have beeninvestigated as antimicrobial agents for the control of gingivitisand/or oral malodor. The antimicrobial activity of these materials istheorized to be linked to the cationic charge(s) of the molecule. Thischarge is attracted to negatively-charged moieties on the cell membraneor wall of the microorganism, and facilitates attachment to the surfaceof the microorganism. The attachment and subsequent interaction with thecell surface disrupts the cell membrane structure, causing leakage ofthe intracellular fluids, eventually killing the microorganism. However,such materials are generally not effective when formulated incombination with anionic materials and when other cationic minerals andorganic molecules present in hard water which may interfere withattraction and subsequent attachment of the cationic materials to thenegatively-charged moieties. These chemical interactions may therebyreduce the overall antimicrobial efficacy of this class of compounds.Noncationic antimicrobial materials, on the other hand can be compatiblewith anionic components of an oral antimicrobial composition or othertype of compositions containing an antimicrobial agent.

[0013] Halogenated hydroxydiphenyl ethers such as triclosan have beeneffectively employed in oral compositions as antimicrobial agents.However, halogenated compounds may present safety issues.

[0014] Alternatives to triclosan with similar antimicrobial activityhave been the subject of continuing investigation. Alkyl substitutedphenols, such as thymol (2-isopropyl-5-methyl phenol), are well knownand widely used as antimicrobials. In combination with menthol,eucalyptol, and methyl salicylate, thymol is an active antimicrobialagent, for example, in commercial clinically effectiveanti-plaque-anti-gingivitis mouthrinse formulations. However, suchessential oil formulations possess lower antimicrobial potency thanthose containing triclosan. Non-halogenated alternatives to triclosanwith similar or improved antimicrobial activity have been the subject ofinventors' investigation.

[0015] Accordingly, it would be a significant advance in the art ofpersonal and dental hygiene to provide new non-halogenated nonionicantimicrobial compounds and compositions containing such compounds whichexhibit substantial antimicrobial effectiveness and yet do not possessthe safety concerns often associated with halogenated compounds such astriclosan.

SUMMARY OF THE INVENTION

[0016] 2. In accordance with the present invention, non-halogenatednaphthol compounds exhibiting effective antimicrobial activity aredisclosed. In one aspect of the invention, the non-halogenated naphtholcompounds are disclosed having the Formula

[0017] wherein

[0018] one of R₁ and R₂ is hydroxyl, and the other of R₁ and R₂ isselected from the group consisting of hydrogen, an alkyl groupoptionally substituted with hydroxyl, a cycloalkyl group optionallysubstituted with hydroxyl, and an hydroxyphenyl group;

[0019] R₃ is selected from the group consisting of hydrogen and an alkylgroup optionally substituted with hydroxyl;

[0020] R₄ is selected from the group consisting of hydrogen, a C₂ to C₆straight chain or branched alkyl group optionally substituted withhydroxyl, a hydroxycycloalkyl group, and,

[0021] wherein

[0022] R_(x) is an alkyl group;

[0023] R₅ is selected from hydrogen, an alkyl group optionallysubstituted with hydroxyl, a cycloalkyl group, a cycloalkenyl group, analkyl group substituted with phenyl, benzyl substituted with an alkylgroup, and,

[0024] wherein R_(x) is an alkyl group;

[0025] each of R₆ and R₇ are selected from the group consisting ofstraight chain or branched alkyl optionally substituted with hydroxyl,and benzy or phenyl optionally substituted with hydroxyl, alkyl, oralkoxy groups;

[0026] with the proviso that:

[0027] when R₁ is hydroxyl, then R₂, R₃, R₄, and R₅ are not allhydrogen;

[0028] when R₂ is hydroxyl, then R₁, R₃, R₄, and R₅ are not allhydrogen;

[0029] when R₂ is hydroxyl, then R₅ is not methyl;

[0030] when R₂ is hydroxyl and each of R₃, R₄, and R₅ is hydrogen, thenR₁ is not selected from the group consisting of isopropyl and isobutyl;

[0031] when R₁ is hydroxyl and each of R₃, R₄ and R₅ is hydrogen, thenR₂ is not 4-hydroxyphenyl; and

[0032] when R₁ is hydroxyl and each of R₃, and R₅ is hydrogen, then R₂and R₄ are not both tert-butyl; and

[0033] with the further proviso that R₆ and R₇ are not both tert-butyl.

[0034] In another aspect of the present invention, an antimicrobialcomposition comprising an effective amount of one or more antimicrobialagents includes non-halogenated naphthol compounds for reducing thepresence of microorganisms on a substrate or in a fluid environment incombination with an effective carrier. In a further aspect of theinvention there is provided an oral antimicrobial composition comprisingan orally acceptable carrier, and an effective antimicrobial amount ofone or more antimicrobial agents including non-halogenated naphtholcompounds for reducing the presence of microorganisms in an oral cavity.

[0035] In one aspect of the present invention there is provided anantimicrobial composition comprising an antimicrobial effective amountof at least one antimicrobial agent having the Formula:

[0036] wherein

[0037] one of R₁ and R₂ is hydroxyl, and the other of R₁ and R₂, andeach of R₃, R₄, and R₅ are independently selected from the groupconsisting of hydrogen; hydroxyl; an alkyl group optionally substitutedwith hydroxyl; an alkenyl group; a cycloalkenyl group; an alkyl groupsubstituted with phenyl in which the phenyl may be substituted with amember selected from the group consisting of an alkyl group optionallysubstituted with hydroxyl and a cycloalkyl group optionally substitutedwith hydroxyl; a cycloalkyl group optionally substituted with hydroxyl;phenyl; phenyl substituted with a member selected from the groupconsisting of an alkyl group optionally substituted with hydroxyl, acycloalkyl group optionally substituted with hydroxyl, and an alkoxygroup; and,

[0038] wherein R_(x) is a member selected from the group consisting ofan alkyl group, benzyl, and phenyl;

[0039] and each of R₆ and R₇ are selected from the group consisting ofstraight chain or branched alkyl groups optionally substituted withhydroxyl, benzyl, and phenyl optionally substituted with alkyl or alkoxygroups;

[0040] with the proviso that:

[0041] when R₁ is hydroxyl, then R₂, R₃, R₄, and R₅ are not allhydrogen;

[0042] when R₂ is hydroxyl, then R₁, R₃, R₄, and R₅ are not allhydrogen;

[0043] when R₁ is hydroxyl, and each of R₃ and R₅ is hydrogen, then R₂and R₄ are not independently selected from methyl and hydrogen;

[0044] when R₂ is hydroxyl, and each of R₁, R₃, R₄ is hydrogen, then R₅is not methyl;

[0045] when R₁ is hydroxyl, and each of R₃, R₄ and R₅ is hydrogen, thenR₂ is not isobutyl; and

[0046] when R₂ is hydroxyl and each of R₃, R₄, and R₅ is hydrogen, thenR₁ is not selected from the group consisting of isopropyl and isobutyl;

[0047] with the further proviso that R₆ and R₇ are not both tert-butyl;and an antimicrobial effective carrier.

[0048] In another aspect, the present invention is directed to an oralcomposition comprising an antimicrobial effective amount of at least oneantimicrobial agent having the Formula

[0049] wherein

[0050] one of R₁ and R₂ is hydroxyl, and the other of R₁ and R₂, andeach of R₃, R₄, and R₅ are independently selected from the groupconsisting of hydrogen; hydroxyl; an alkyl group optionally substitutedwith hydroxyl; an alkenyl group; a cycloalkenyl group; an alkyl groupsubstituted with phenyl in which the phenyl may be substituted with amember selected from the group consisting of an alkyl group optionallysubstituted with hydroxyl and a cycloalkyl group optionally substitutedwith hydroxyl; a cycloalkyl group optionally substituted with hydroxyl;phenyl; phenyl substituted with a member selected from the groupconsisting of an alkyl group optionally substituted with hydroxyl, acycloalkyl group optionally substituted with hydroxyl, and an alkoxygroup; and,

[0051] wherein R_(x) is a member selected from the group consisting ofan alkyl group, benzyl, and phenyl; and each of R₆ and R₇ are selectedfrom the group consisting of straight chain or branched alkyl optionallysubstituted with hydroxyl, and benzyl or phenyl optionally substitutedwith hydroxyl, alkyl, or alkoxy groups;

[0052] with the proviso that:

[0053] when R₁ is hydroxyl, then R₂, R₃, R₄, and R₅ are not allhydrogen;

[0054] when R₂ is hydroxyl, then R₁, R₃, R₄, and R₅ are not allhydrogen; and

[0055] an orally acceptable carrier.

DETAILED DESCRIPTION OF THE INVENTION

[0056] The present invention is directed to non-halogenated naphtholcompounds which exhibit effective antimicrobial activities in a varietyof compositions and applications while maintaining a positive safetyprofile desirable for human use. The antimicrobial activity of thecompounds of the present invention are much improved over thoseexhibited by prior art antimicrobial compounds. Since the novelcompounds are composed entirely of hydrocarbon constituents with ahydroxyl substitutent, such compounds are significantly safer than priorart antimicrobial compounds such as halogenated naphthols, for example.More specifically, the novel compounds include one or more substitutentswhich substantially improves overall antimicrobial activity foreffectively reducing the presence of microorganisms.

[0057] The present invention is further directed to an antimicrobialcomposition effective in treating various substrate surfaces includingthe oral cavity which may contain microorganisms. The antimicrobialcomposition is especially effective against microorganisms residing inthe oral cavity responsible for bad breath, plaque and/or calculus, andthe resulting tooth and gum diseases that may be caused thereby. Theantimicrobial composition is effective yet is safe to use.

[0058] Accordingly, the present invention provides for non-halogenatednaphthol compounds exhibiting antimicrobial activities which arerepresented by Formula:

[0059] wherein

[0060] one of R₁ and R₂ is hydroxyl, and the other of R₁ and R₂ isselected from the group consisting of hydrogen, an alkyl groupoptionally substituted with hydroxyl, a cycloalkyl group optionallysubstituted with hydroxyl, and an hydroxyphenyl group;

[0061] R₃ is selected from the group consisting of hydrogen and an alkylgroup optionally substituted with hydroxyl;

[0062] R₄ is selected from the group consisting of hydrogen, a C₂ to C₆straight chain or branched alkyl group optionally substituted withhydroxyl, a hydroxycycloalkyl group, and,

[0063] wherein R_(x) is an alkyl group;

[0064] R₅ is selected from hydrogen, an alkyl group optionallysubstituted with hydroxyl, a cycloalkyl group, a cycloalkenyl group, analkyl group substituted with phenyl, benzyl substituted with an alkylgroup, and,

[0065] wherein R_(x) is an alkyl group;

[0066] each of R₆ and R₇ are selected from the group consisting ofstraight chain or branched alkyl optionally substituted with hydroxyl,and benzyl or phenyl optionally substituted with hydroxyl, alkyl, oralkoxy groups;

[0067] with the proviso that:

[0068] when R₁ is hydroxyl, then R₂, R₃, R₄, and R₅ are not allhydrogen;

[0069] when R₂ is hydroxyl, then R₁, R₃, R₄, and R₅ are not allhydrogen;

[0070] when R₂ is hydroxyl, then R₅ is not methyl;

[0071] when R₂ is hydroxyl and each of R₃, R₄, and R₅ is hydrogen, thenR₁ is not selected from the group consisting of isopropyl and isobutyl;

[0072] when R₁ is hydroxyl and each of R₃, R₄ and R₅ is hydrogen, thenR₂ is not 4-hydroxyphenyl; and

[0073] when R₁ is hydroxyl and each of R₃, and R₅ is hydrogen, then R₂and R₄ are not both tert-butyl;

[0074] with the further proviso that R₆ and R₇ are not both tert-butyl.

[0075] A particularly preferred group of compounds exhibitingantimicrobial properties includes3-isopropyl-6-(1-methyl-butyl)-naphthalen-2-ol,3-isopropyl-6-(1-phenyl-ethyl)-naphthalen-2-ol,1-(4-hydroxynaphthyl)octan-1-one,6-(1-ethyl-1-methyl-propyl)-1-isopropyl-naphthalen-2-ol,6-(tert-butyl)-1-isoproyl-naphthalen-2-ol,6-(3-cyclohexenyl)-2-naphthol, 1-(6-hydroxy-2-naphthyl)hexan-1-one,1-isopropyl-6-(3-methyl-benzyl)-naphthalen-2-ol,1-(4-hydroxynaphthyl)hexan-1-one,6-cyclohex-2-enyl-3-isopropyl-naphthalen-2-ol, 6-cyclopentyl-2-naphthol,6-(1-ethyl-1-metyl-propyl)-3-isopropyl-naphthalen-2-ol,3-isopropyl-6-(3-methyl-benzyl)naphthalen-2-ol,6-(tert-butyl)-1-isopropyl-naphthalen-2-ol,6-(3-methyl-benzyl)-2-naphthol, 4-(2-hydroxycyclohexyl)-1-naphthol,4-(3-hydroxycyclohexyl)-1-naphthol, 1-(2-hydroxycyclohexyl)-2-naphthol,1-(3-hydroxycyclohexyl)-2-naphthol, 1-(4-hydroxycyclohexyl)-2-naphthol,1-cyclopentyl-2-naphthol, 1-(2-hydroxycyclopentyl)-2-naphtol,1-(3-hydroxycyclopentyl)-2-naphthol,4-(2-hydroxycyclopentyl)-1-naphthol, and4-(3-hydroxycyclopentyl)-1-naphthol.

[0076] The present invention further provides for preferred compositionscomprising an antimicrobial effective amount of one or moreantimicrobial agents having Formula:

[0077] wherein

[0078] one of R₁ and R₂ is hydroxyl, and the other of R₁ and R₂, andeach of R₃, R₄, and R₅ are independently selected from the groupconsisting of hydrogen; hydroxyl; an alkyl group optionally substitutedwith hydroxyl; an alkenyl group; a cycloalkenyl group; an alkyl groupsubstituted with phenyl in which the phenyl may be substituted with amember selected from the group consisting of an alkyl group optionallysubstituted with hydroxyl and a cycloalkyl group optionally substitutedwith hydroxyl; a cycloalkyl group optionally substituted with hydroxyl;phenyl; phenyl substituted with a member selected from the groupconsisting of an alkyl group optionally substituted with hydroxyl, acycloalkyl group optionally substituted with hydroxyl, and an alkoxygroup; and,

[0079] wherein R_(x) is a member selected from the group consisting ofan alkyl group, benzyl, and phenyl; and each of R₆ and R₇ are selectedfrom the group consisting of straight chain or branched alkyl optionallysubstituted with hydroxyl, and benzyl or phenyl optionally substitutedwith hydroxyl, alkyl, or alkoxy groups;

[0080] with the proviso that:

[0081] when R₁ is hydroxyl, then R₂, R₃, R₄, and R₅ are not allhydrogen;

[0082] when R₂ is hydroxyl, then R₁, R₃, R₄, and R₅ are not allhydrogen;

[0083] when R₁ is hydroxyl, and each of R₃ and R₅ is hydrogen, then R₂and R₄ are not independently selected from methyl and hydrogen;

[0084] when R₂ is hydroxyl, and each of R₁, R₃, R₄ is hydrogen, then R₅is not methyl;

[0085] when R₁ is hydroxyl, and each of R₃, R₄ and R₅ is hydrogen, thenR₂ is not isobutyl; and

[0086] when R₂ is hydroxyl and each of R₃, R₄, and R₅ is hydrogen, thenR₁ is not selected from the group consisting of isopropyl and isobutyl;

[0087] with the further proviso that R₆ and R₇ are not both tert-butyl;and an antimicrobial effective carrier.

[0088] The above antimicrobial agents of Formula (II), are incorporatedin an antimicrobial composition of the present invention in an amount ofabout 0.0001 to 10% by weight, preferably from about 0.001 to 5% byweight.

[0089] A particularly preferred group of antimicrobial agents includes1-(2-hydroxyphenyl)naphthalen-2-ol,6-(tert-butyl)-1-isopropyl-naphthalen-2-ol,6-(3-cyclohexenyl)-2-naphthol, 6-cyclopentyl-2-naphthol,6-(3-methylbenzyl)-2-naphthol,1-Isopropyl-6-(3-methyl-benzyl)-naphthalen-1-ol,3-Isopropyl-6-(1-phenyl-ethyl)-naphthalen-2-ol,6-(1-Ethyl-1-methyl-propyl)-3-isopropyl-naphthalen-2-ol,6-Cyclohex-2-enyl-3-isopropyl-naphthalen-2-ol,3-Isopropyl-6-(3-methyl-benzyl)-naphthalen-2-ol,3-Isopropyl-6-(1-methyl-butyl)-naphthalen-2-ol,1-(4-Hydroxy-cyclohexyl)-naphthalen-2-ol, 1-Cyclopentyl-naphthalen-2-ol,3-(1-Ethyl-1-hydroxy-propyl)-naphthalen-2-ol,1-hydroxyhexyl)naphthalen-2-ol,6-Hydroxymethyl-1-phenyl-naphthalen-2-ol, 2-tert-butyl-1-naphthol,4-tert-butyl-1-naphthol, 2,4-bis-tert-butyl-1-naphthol,4-benzyl-1-naphthol, 3-isopropyl-2-naphthol, 1-butyl-2-naphthol,1-tert-butyl-2-naphthol, 1-hexyl-2-naphthol, 1-cyclohexyl-2-naphthol,1-(3-hydroxycyclohexyl)-2-naphthol, 1-phenyl-2-naphthol, and1-benzyl-2-naphthol.

[0090] The present invention also provides a method of reducing thepresence of microorganisms on a substrate comprising treating thesubstrate with an antimicrobial effective amount of at least oneantimicrobial agent having Formula (II).

[0091] The antimicrobial compositions of the present invention may beincorporated into products having a variety of vehicles for applicationto the skin or tissue surfaces including creams, lotions, foundations,cleansing lotions, soaps, shampoos, ointments, syrups and suspensions.Compositions may comprise, for example, aqueous or oily solutions ordispersions, oil-in-water or water-in-oil emulsions, pastes, gels orsolids. Topically or orally acceptable carriers and excipients of use insuch preparations will be well known to those skilled in the art.

[0092] The anti-microbial compositions of the present invention may beincluded in products which are developed for the treatment ofmicroorganism-instigated conditions such as deodorant and/orantiperspirant preparations, antibacterial skin washes, anti-acnepreparations, impregnated materials (e.g. wound dressings, sutures, anddental floss), pharmaceuticals, opthalmic preparations and sterilants.

[0093] Typically, a deodorizing composition reduces or prevent body odorby reducing perspiration (e.g. often referred to as an antiperspirantcomposition) or the presence of microorganisms on the surface of theskin.

[0094] Antiperspirant compositions often comprise a metal salt, such asaluminum or zirconium salts which blocks the pores of the skin.Typically, such compositions, however, reduce perspiration by no morethan 50%. It is well known that sweat is odorless until it has beendegraded by the skin microflora. Typical deodorant compositions includeethanol and/or Triclosan (2′,4,4′-trichloro,2-hydroxy-diphenyl ether)which are a well known antimicrobial agents. However, the deodorizingeffect obtained with such deodorant compositions is transitory and theconcentration of microorganisms may reach previous levels shortly afterapplication.

[0095] The invention provides a deodorant composition for topicalapplication to human skin comprising at least one antimicrobial agenthaving Formula (II) in an acceptable carrier in which the composition isat least reduces the presence of microorganisms and/or their malodorousmetabolic processes for greater than a transitory period of time.

[0096] Such deodorant compositions in addition to containing thecomposition of the present invention may contain a low molecular weightaliphatic alcohol, preferably containing up to 4 carbons and especiallya monohydric alcohol such as ethanol, which can act in combination withthe antimicrobial agents of Formula (II) to provide an effectivedeodorant composition. The amount of the alcohol in the composition istypically selected within the range of from about 10 to 80% by weight,preferably from about 30 to 70% by weight.

[0097] The deodorant composition according to the present invention mayalso comprise other materials commonly found in deodorant orantiperspirant compositions. In practice, the present compositionusually contains at least one acceptable carrier in addition to theantimicrobial agent of Formula (II) alone or in combination with analcohol. The carrier may comprise a liquid vehicle such as an alcohol asdescribed hereinbefore, in addition to water, a hydrophobic vehiclewhich may for example be a volatile or non-volatile silicone oil, aliquid hydrocarbon, a water-insoluble alcohol, an aliphatic ether, analiphatic or aromatic ester. The carrier is typically present in anamount of from about 10 to 80% by weight based on the total weight ofthe composition.

[0098] Other additives may include perfumes in an amount of from about 0to 2% by weight, antiperspirant actives such as aluminum or zirconiumcompounds in an amount of from about 0 to 40% by weight, preferably fromabout 5 to 28% by weight, skin softening agents such as silicone oils orsolid silicone polymers, in an amount of from about 0 to 20% by weight,coloring agents in an amount of from about 0 to 2% by weight,humectants, such as sorbitol or glycerol, in an amount of from about 0to 10% by weight, thickening agents such as starches or cellulosederivatives, in an amount from about 0 to 5% by weight, gellants such asdibenzoyl sorbitol, hydroxystearic acid, stearyl alcohol, or amidederivatives of tricarboxylic acids, in an amount of from about 0 to 15%by weight, suspension agents, such as clays or silicas, in an amount ofup to about 5% by weight, structurants such as silicone elastomers orsilicone or hydrocarbon waxes, in an amount of about 0 to 15% by weight,propellants, such as hydrocarbons having a boiling point of below 10EC., e.g. butane and propane isomers, in an amount of from about 30 to95% by weight, and other cosmetic additives conventionally employed insuch compositions. Where water and a hydrophobic material is present,the composition preferably contains an emulsifier/system such aspolyethoxylate ethers or esters. The use of such substances and theproportions in which they are incorporated depend on the form of thecomposition which may be an aerosol, stick, roll-on, gel, lotion, cream,ointment, powder, suspension or soap.

[0099] Gels are transparent, semi-solid, colloidal systems where thewater is restricted by an interlacing network of solvated particles. Thegels useful in the present invention may have a wide range ofviscosities, e.g., from about 4,000 to about 200,000 centipoise,however, since they are formulated for topical use, the compositionswill generally have relatively high viscosities (i.e., they will beself-supporting).

[0100] The formulation of aqueous gels requires the presence of waterand generally requires the use of a compatiblepharmaceutically-acceptable gelling agent in the compositions of thepresent invention. Preferred compositions contain at least about 15%water, and may additionally contain an alcohol or mixture of alcohols(e.g., C₁-C₁₄) in a water:alcohol ratio of from about 5:1 to about100:1. The gelling agent will generally be present at about 0.25% toabout 10% of the composition. Desirable gels may be formed using anacidic carboxy polymer as the gelling agent, together with a compatibleneutralizing agent. Pharmaceutically-acceptable acidic carboxy polymersinclude, for example, Carbopol compounds (a range of carboxypolymethylenes commercially available from B. F. Goodrich Chemicals,Cleveland, Ohio) and the neutralizing compounds include, for example,diisopropyl amine, sodium hydroxide, and beta-alanine. Surface activeagents or surfactants, especially nonionic surfactants, such as ethyleneoxide/propylene oxide block copolymers (commercially available asPluronics from BASF Wyandotte Corp.), and/or ethylene glycol orpropylene glycol may also be included in the compositions to help in theformation of the gel and to act as dispersing agents for the activecomponents.

[0101] Aqueous lotions of the present invention are formulated in thesame way as the above-described gels, except that they have lowerviscosities (i.e., below about 4,000 centipoise) and do not include thegelling agent. Lotions are liquid preparations intended for externalapplication to the skin. Most lotions contain finely powdered substancesthat are insoluble in the dispersion medium and are suspended throughthe use of suspending or dispersing agents. Other lotions have, as thedispersed liquid phase, liquid substances that are immiscible with thevehicle and are usually dispersed by means of emulsifying agents orother suitable stabilizers. Depending upon the nature of theingredients, lotions may be prepared in the same manner as suspensions,emulsions or solutions. The fluidity of lotions permits their rapid anduniform application over a wide surface area.

[0102] The compositions of the present invention may additionallycontain, at their art-established usage levels, compatible adjunctcomponents conventionally used in the formulation of topicalcompositions. These adjunct components include, but are not limited to,active materials (such as supplementary antimicrobial oranti-inflammatory ingredients) or ingredients used to enhance theformulation, itself (such as excipients, dyes, perfumes, thickeningagents, skin penetration enhancers, stabilizers, preservatives, andantioxidants). The compositions of the present invention may alsocontain, in an amount which can range from about 1% to about 99.5% ofthe compositions, compatible pharmaceutical carrier materials especiallyadapted for topical application and formulation into an aqueous lotionor gel. Carrier materials suitable for use in the instant compositionsinclude those well-known for use in the cosmetic and medical arts.Suitable carriers include, for example, water, liquid alcohols, liquidglycols, liquid polyalkalene glycols, liquid esters, liquid amines,liquid protein hydrolysates, liquid alkalated protein hydrolysates,liquid lanolin and lanolin derivatives, and like materials.

[0103] More preferred compositions include those represented for use inan oral cavity comprise an antimicrobial effective amount of one or moreantimicrobial agents having Formula

[0104] wherein

[0105] one of R₁ and R₂ is hydroxyl, and the other of R₁ and R₂, andeach of R₃, R₄, and R₅ are independently selected from the groupconsisting of hydrogen; hydroxyl; an alkyl group optionally substitutedwith hydroxyl; an alkenyl group; a cycloalkenyl group; an alkyl groupsubstituted with phenyl in which the phenyl may be substituted with amember selected from the group consisting of an alkyl group optionallysubstituted with hydroxyl and a cycloalkyl group optionally substitutedwith hydroxyl; a cycloalkyl group optionally substituted with hydroxyl;phenyl; phenyl substituted with a member selected from the groupconsisting of an alkyl group optionally substituted with hydroxyl, acycloalkyl group optionally substituted with hydroxyl, and an alkoxygroup; and,

[0106] wherein R_(x) is a member selected from the group consisting ofan alkyl group, benzyl, and phenyl; and each of R₆ and R₇ are selectedfrom the group consisting of straight chain or branched alkyl optionallysubstituted with hydroxyl, and benzyl or phenyl optionally substitutedwith hydroxyl, alkyl, or alkoxy groups;

[0107] with the proviso that:

[0108] when R₁ is hydroxyl, then R₂, R₃, R₄, and R₅ are not allhydrogen;

[0109] when R₂ is hydroxyl, then R₁, R₃, R₄, and R₅ are not allhydrogen; and

[0110] an orally acceptable carrier.

[0111] The present invention further provides a method of reducingmicroorganisms in an oral cavity which comprises administering to theoral cavity an oral antimicrobial composition having an effective amountof at least one antimicrobial agent of Formula (III).

[0112] A particularly preferred group of antimicrobial agents for oralcomposition includes 1-(2-hydroxyphenyl)naphthalen-2-ol,6-(tert-butyl)-1-isopropyl-naphthalen-2-ol,6-(3-cyclohexenyl)-2-naphthol, 6-cyclopentyl-2-naphthol,6-(3-methylbenzyl)-2-naphthol,1-Isopropyl-6-(3-methyl-benzyl)-naphthalen-2-ol,3-Isopropyl-6-(1-phenyl-ethyl)-naphthalen-2-ol,6-(1-Ethyl-1-methyl-propyl)-3isopropyl-naphthalen-2-ol,6-Cyclohex-2-enyl-3-isopropyl-naphthalen-2-ol,3-Isopropyl-6-(3-methyl-benzyl)-naphthalen-2-ol,3-Isopropyl-6-(1-methyl-butyl)-naphthalen-2-ol,1-(4-Hydroxy-cyclohexyl)-naphthalen-2-ol, 1-Cyclopentyl-naphthalen-2-ol,3-(1-Ethyl-1-hydroxy-propyl)-naphthalen-2-ol,1-(6-hydroxyhexyl)naphthalen-2-ol,6-Hydroxymethyl-1-phenyl-naphthalen-2-ol, 2-tert-butyl-1-naphthol,4-tert-butyl-1-naphthol, 2,4-bis-tert-butyl-1-naphthol, and4-benzyl-1-naphthol, 1-isopropyl-2-naphthol, 3-isopropyl-2-naphthol,1-butyl-2-naphthol, 1-tert-butyl-2-naphthol, 1-hexyl-2-naphthol,1-cyclohexyl-2-naphthol, 1-(3-hydroxycyclohexyl)-2-naphthol,1-phenyl-2-naphthol, and 1-benzyl-2-naphthol.

[0113] The antimicrobial agents of Formula (III) may be present in anoral composition of the present invention in an amount of from about0.0001 to 10% by weight, preferably from about 0.001 to about 5% byweight.

[0114] The use of the anti-microbial compositions according to theinvention in oral composition is particularly advantageous because theyprovide effective results against a broad range of microorganisms knownto be present in the oral cavity.

[0115] Oral compositions which contain antimicrobial compounds of thepresent invention may be in the form of mouthwashes, gargles,dentifrices, anti-plaque compositions, dispersible oral films, and asgeneral antiseptic compositions, for example, in the form of denturecleansing tablets or solutions. The oral compositions of the presentinvention may, if desired, further comprise one or more additionalactive ingredients and formulations containing such, as conventionallyused in the art. These include, for example, anti-plaque agents such asbromochlorophene, triclosan, cetylpyridinium chloride, chlorhexidinesalts, and essential oils such as thymol, menthol, and the like,fluoride ion sources such as sodium fluoride, sodium monofluorophosphateand amine fluorides, anti-tartar agents such as zinc salts, preferablyzinc citrate, and water soluble pyrophosphate salts, preferably alkalimetal pyrophosphates, and desensitizing agents which reduce toothsensitivity including potassium salts such as potassium nitrate andpotassium chloride and strontium salts such as strontium chloride andstrontium acetate.

[0116] One particular formulation comprising essential oils is soldcommercially as LISTERINE® which composition is exemplified in Pan etal. (U.S. Pat. No. 6,121,315), and which reference includes effectiveessential oil formulations having anti-plaque activity. The contents ofU.S. Pat. No. 6,121,315 is hereby incorporated by reference in itsentirety. The essential oil formulation preferably comprises from about0.005% to 0.5% by weight of thymol, from about 0.005% to 0.5% by weightof menthol, from about 0.005% to 0.5% by weight of eucalyptol, and fromabout 0.005% to 0.5% by weight of methyl salicylate.

[0117] The compositions according to the invention may alternatively beprovided in concentrated form, for example as a powder, anhydroussolution or effervescent tablet formulation, suitable for dilution inwater prior to use as a sterilant of, for example, dental instruments.One preferred use of the anti-microbial compositions of the invention isas toothbrush sanitizers, designed to reduce microbiologicalcontamination of toothbrush heads, for example by overnight soaking asneeded, typically every 1 to 14 days of use. A substantial reduction inmicroorganism contamination may be achieved in this way withoutsignificant adverse effects on the toothbrush or other dentalinstrument.

[0118] Antimicrobial enhancing agent(s) may be included in the oralcompositions of the present invention. Incorporating such antimicrobialenhancing agent into compositions containing antimicrobial compounds areknown in the art, as described for example in U.S. Pat. Nos. 5,188,821and 5,192,531. The term “antimicrobial enhancing agent” as used hereinrefers to organic compounds which contains a delivery-enhancing groupand a retention-enhancing group which together act to improve thesanitizing effectiveness of the antimicrobial agent. As used herein, thedelivery-enhancing group refers to one which attaches or substantively,adhesively, cohesively or otherwise bonds the antimicrobial enhancingagent (carrying the antimicrobial agent) to oral surfaces such as toothand gum, thereby “delivering” the antimicrobial agent to such surfaces.The retention-enhancing group, generally hydrophobic, attaches orotherwise bonds the antimicrobial agent to the antimicrobial enhancingagent, thereby promoting retention of the antimicrobial agent to theantimicrobial enhancing agent and indirectly on the oral surfaces. Theactive retention of the antimicrobial agent on the oral surfacesenhances the disinfecting effect on oral surfaces.

[0119] In the preferred form, the antimicrobial enhancing agent includesan anionic polymer comprising a chain or backbone containing repeatingunits each preferably containing at least one carbon atom and preferablyat least one directly or indirectly pendent, monovalentdelivery-enhancing group, and at least one directly or indirectlypendent, monovalent retention-enhancing group geminally, vincinally, orless preferably otherwise bonded to atoms, preferably carbon, in thechain.

[0120] The antimicrobial enhancing agent may be a simple compound suchas a polymerizable monomer, or more preferably a polymer includingoligomers, homopolymers, copolymers of two or more monomers, ionomers,block copolymers, graft copolymers, cross-linked polymers andcopolymers, and the like. The antimicrobial enhancing agent may benatural or synthetic, and water-insoluble or preferably water soluble orswellable, having an average molecular weight of from about 100 to5,000,000, preferably from about 1,000 to 1,000,000, more preferablyfrom about 25,000 to 500,000.

[0121] Preferable antimicrobial enhancing agents for use in the practiceof the present invention include a natural or synthetic anionicpolymeric polycarboxylate having a molecular weight of from about 1,000to 5,000,000, preferably from about 30,000 to 500,000. Synthetic anionicpolymeric polycarboxylates are generally employed in the form of theirfree acids or preferably partially or more preferably fully neutralizedwater soluble alkali metal such as potassium and sodium, or ammoniumsalts. Preferred are 1:4 to 4:1 copolymers of maleic anhydride or acidwith another polymerizable ethylenically unsaturated monomer, preferablymethyl vinyl ether/maleic anhydride having a molecular weight of fromabout 30,000 to 1,000,000, most preferably from about 30,000 to 500,000.These copolymers are available, for example, as GANTREZ®, AN 139(molecular weight 500,000), AN 119 (molecular weight 250,000), andpreferably S-97 Pharmaceutical Grade (molecular weight 700,000), fromISP Technologies, Inc., Bound Brook, N.J. 08805.

[0122] Other useful polymeric polycarboxylates containing or modified tocontain retention-enhancing groups include the 1:1 copolymers of maleicanhydride with ethyl acrylate, hydroxyethyl methacrylate,N-vinyl-2-pyrollidone, or ethylene, the latter being available, forexample, as Monsanto EMA® No. 1103 (molecular weight 10,000), and Grade61, and 1:1 copolymers of acrylic acid with methyl or hydroxyethylmethacrylate, methyl or ethyl acrylate, isobutyl methacrylate, isobutylvinyl ether or N-vinyl-2-pyrrolidone. Additional polycarboxylatecompounds containing or modified to contain retention-enhancing groupsinclude copolymers of maleic anhydride with styrene, isobutylene orethyl vinyl ether, polyacrylic, polyitaconic and polymaleic acids, andsulfonacrylic oligomers with a molecular weight as low as 1,000available as UNIROYAL® ND-2.

[0123] Also useful in the practice of the present invention are theso-called carboxyvinyl polymers, commercially available, for example,under the trademarks CARBOPOL® 934, 940, and 941 from B. F. Goodrich,Cleveland, Ohio 44131, these polymers consisting of a colloidallywater-soluble polymer of polyacrylic acid crosslinked with from about0.75% to about 2.0% of polyallyl sucrose or polyallyl pentaerythritol asa crosslinking agent, often with molecular weights of up to 4-5 millionor more.

[0124] Polysiloxanes containing or modified to contain pendentdelivery-enhancing groups and retention-enhancing groups such as liquidsilicone oils such as diphenyl or di(C₁-C₄)alkyl polysiloxanes andparticularly dimethyl-polysiloxane, may also be employed in the practiceof the present invention.

[0125] Also effective herein are ionomers containing or modified tocontain delivery- and retention-enhancing groups. Ionomers are describedon pages 546-573 of the Kirk Othmer Encyclopedia of Chemical Technology,Third Edition, Supplement Volume, John Wiley & Sons, copyright 1984,which description is incorporated herein by reference. Also effectiveherein, provided that contain or are modified to containingretention-enhancing groups, are polyesters, polyurethanes, and syntheticand natural polyamides including proteins and proteinaceous materialssuch as collagen, poly(arginine) and other polymerized amino acids.

[0126] The antimicrobial enhancing agent, when employed, is incorporatedin the compositions of the present invention in weight amounts of fromabout 0.05 to about 5%, preferably from about 0.1 to 3%.

[0127] Fluoride ions may also be included in the oral compositions ofthe present invention. Fluoride ions are implicated in the prevention ofdental caries and may also serve as a tooth-hardening agent. An amountof fluoride ions suitable for use in an oral composition of the presentinvention is from 25 ppm to 5,000 ppm.

[0128] Fluoride ion producing compounds vary in degree of watersolubility. They release fluoride ions in water and do not generallyreact with other compounds of the oral composition. Among the fluorideion producing compounds are inorganic fluoride salts, such as solublealkali metal, alkaline earth metal salts, for example, sodium fluoride,potassium fluoride, ammonium fluoride, calcium fluoride, cuprousfluoride, zinc fluoride, barium fluoride, sodium monofluorophosphate,aluminum mono-and di-fluorophosphate and sodium calcium fluorophosphate.Alkali metal and tin fluorides, such as sodium and stannous fluorides,sodium monofluorophosphate (MFP) and mixtures thereof, are preferred.

[0129] The amount of fluoride ion producing compound is dependent uponthe type of compound, its solubility in water, and the type of oralcomposition. A non-toxic amount of such compound is generally in therange from about 0.0005 to 3.0% by weight based on the total weight ofthe oral composition. Any suitable minimum amount of such compounds maybe used, but it is preferable to employ a sufficient amount of thefluoride ion producing compounds to provide from about 300 to 2,000 ppm,more preferably from about 800 to about 1,500 ppm of fluoride ion to theoral cavity.

[0130] Typically, for sodium fluoride, the desired amount up to about 2%by weight, based on the total weight of the composition, and preferablyin an amount of from about 0.05 to 1%, more preferably from about 0.2 to0.35% by weight. Typically for sodium monofluorophosphate, the compoundis desirably present in an amount of from about 0.1 to 3%, morepreferably about 0.76% by weight.

[0131] The oral composition of the present invention may be in the formof a solution such as a mouthrinse and may be in the form of asemi-solid such as a toothpaste, a gel dentifrice (which may containfrom about 0 to 75% by weight of a polishing agent), a chewing gum, adispersible oral film, a film-forming dentifrice, a solid lozenge or thelike.

[0132] Oral gel preparations typically contain a siliceous polishingmaterial including crystalline silica having particle sizes of up to 5microns, silica gel, colloidal silica or complex amorphous alkali metalaluminosilicate or combinations thereof. When visually clear oropacified gels are employed, a polishing agent of colloidal silica oralkali metal aluminosilicate complexes (that is, silica containingalumina combined in its matrix) are particularly useful, since they areconsistent with gel-like texture and have refractive indices close tothe refractive indices of gelling agent-liquid (including water and/orhumectant) systems commonly used in dentifrices.

[0133] Where the oral composition of the present invention is a gel orpaste, an orally acceptable carrier, including a water-phase withhumectant which is preferably glycerine or sorbitol or an alkyleneglycol such as polyethylene glycol or propylene glycol is present. Wherewater is typically present in an amount of from about 15 to 40% byweight and glycerine, sorbitol and/or the alkylene glycol (preferablypropylene glycol) are preferably in an amount of from about 20 to 75% byweight, preferably about 25 to 60% by weight based on the total weightof the composition.

[0134] When the oral composition is substantially semi-solid or pasty incharacter, such as a toothpaste (dentifrice), the orally acceptablecarrier of the dentifrice may contain a dentally acceptable polishingmaterial such as sodium bicarbonate, sodium metaphosphate, potassiummetaphosphate, tricalcium phosphate, dihydrated dicalcium phosphate,anhydrous dicalcium phosphate, calcium pyrophosphate, calcium carbonate,aluminum silicate, hydrated alumina, silica, bentonite, and mixturesthereof alone or with minor amounts of hard polishing material such ascalcined alumina and/or zirconium silicate. Preferred polishingmaterials include sodium bicarbonate, silica, sodium metaphosphate,dicalcium phosphate, calcium pyrophosphate and hydrated alumina.

[0135] The polishing material is generally present in the oralcomposition in an amount of from about 10% to 75% by weight, preferablyfrom about 10% to 30% by weight in a gel, and preferably from about 25%to 75% by weight in a cream or paste.

[0136] Toothpastes or dental cream dentifrices as well as geldentifrices typically contain a natural or synthetic thickener orgelling agent in an amount of from about 0.1 to 10% by weight,preferably from about 0.5 to 5% by weight.

[0137] Suitable thickeners or gelling agents include Irish moss,iota-carrageenan, kappa-carrageenan, gum tragacanth, starch,polyvinylpyrrolidone, xantham gum, hydroxyethyl propyl cellulose,hydroxybutyl methyl cellulose, hydroxypropyl methyl cellulose,hydroxyethyl cellulose and sodium carboxymethyl cellulose.

[0138] Where the oral composition is a liquid such as a mouthwash orrinse, the liquid carrier is typically a water-alcohol mixture.Generally, the weight ratio of water to alcohol is in the range of fromabout 3:1 to 20:1 and preferably from about 4:1 to 10:1. The alcohol isa non-toxic alcohol such as ethanol or isopropanol. A humectant such asglycerine, sorbitol or an alkylene glycol such as polyethylene glycol orpreferably propylene glycol may be present in an amount of from about 10to 30% by weight. Mouthrinses typically contain about 50 to 85% ofwater, from about 0 to 20% by weight of a non-toxic alcohol and fromabout 10 to 40% by weight of a humectant.

[0139] Organic surface-active agents may be used in the compositions ofthe present invention to achieve increased antimicrobial action, andassist in achieving thorough and complete dispersion of theantimicrobial agent of Formula (III) throughout the oral cavity. Theorganic surface-active agent is preferably anionic, cationic, nonionicor ampholytic in nature, and imparts to the composition detersive andfoaming properties. Suitable examples of anionic surface-active agentsare water-soluble salts of higher fatty acid monoglyceride monosulfates,such as the sodium salt of the monosulfated monoglyceride ofhydrogenated coconut oil fatty acids, higher alkyl sulfates such assodium lauryl sulfate, alkyl aryl sulfonates such as sodium dodecylbenzene sulfonate, higher alkyl sulfoacetates, higher fatty acid estersof 1,2-dihydroxy propane sulfonate, and the substantially saturatedhigher aliphatic acyl amides of lower aliphatic amino carboxylic acidcompounds, such as those having 12 to 16 carbons in the fatty acid,alkyl or acyl radicals and alkoyl taurines, and the like. Examples ofsuch compounds include N-lauroyl sarcosine, and the sodium, potassiumand ethanolamine salts of N-lauroyl, N-myristoyl, or N-palmitoylsarcosine which are substantially free from soap or similar higher fattyacid material as well as N-methyl-N-cocoyl (or oleoyl or palmitoyl)taurines. The use of sarcosinate compounds in the oral compositions ofthe present invention is typically advantageous since these materialsexhibit a prolonged and marked effect in the inhibition of acidformation in the oral cavity due to carbohydrate breakdown in additionto exerting some reduction in the solubility of tooth enamel in acidsolutions.

[0140] Examples of water-soluble nonionic surface-active agents arecondensation products of ethylene oxide with various reactivehydrogen-containing compounds reactive therewith having long hydrophobicchains (e.g. aliphatic chains of about 12 to 20 carbon atoms), whichcondensation products (“ethoxamers”) contain hydrophilic polyoxyethylenemoieties, such as condensation products of poly (ethylene oxide) withfatty acids, fatty alcohols, fatty amides, polyhydric alcohols (e.g.sorbitan monostearate) and polypropyleneoxide.

[0141] Amphoteric surface active agents have the capacity to behave aseither an acid or a base and include quaternized imidazole derivatives.Preferred amphoteric surfactants include long chain (alkyl)amino-alkylene alkylated amine derivatives, also known as MIRANOL®,manufactured by Rhone-Poulanc, Cranberry, N.J.

[0142] Examples of polyoxamers useful in the practice of the presentinvention include block copolymers of polyoxyethylene andpolyoxypropylene having an average molecular weight of from about 3000to 5000 and a preferred average molecular weight of from about 3500 to4000, and containing from about 10 to 80% by weight of hydrophilicpolyoxyethylene groups of the block copolymer.

[0143] Natural and artificial sweeteners may be used in the oralcompositions. The sweetener may be selected from a wide range of wellknown materials including naturally occurring water-soluble sweeteners,artificial water-soluble sweeteners and modified water-solublesweeteners derived from naturally occurring water-soluble sweeteners.Artificial water-soluble sweeteners include, but are not limited to,soluble saccharin salts, e.g., sodium or calcium saccharin salts,cyclamate salts, the sodium, ammonium or calcium salt of3,4-dihydro-6-methyl-1,2,3-oxathiazine-4-one-2,2-dioxide, the potassiumsalt of 3,4-dihydro-6-methyl-1,2,3-oxathiazine-4-one-2,2-dioxide(Acesulfame-K), the free acid form of saccharin and dipeptide basedsweeteners, such as L-aspartic acid derived sweeteners. Dipeptidesweeteners include L-aspartyl-L-phenylalanine methyl ester (Aspartame)and materials described in U.S. Pat. No. 3,492,131,L-alpha-aspartyl-N-(2,2,4,4-tetramethyl-3-thietanyl)-D-alaninamidehydrate (Alitame), methyl esters of L-aspartyl-L-phenylglycerine andL-aspartyl-L-2,5-dihydrophenylglycine,L-aspartyl-2,5-dihydro-L-phenylalanine andL-aspartyl-L-(1-cyclohexene)-alanine. Naturally occurring water-solublesweeteners include, but are not limited to, sugar alcohols, includingsorbitol as 70% sorbitol solution, mannitol, xylitol, maltitol,hydrogenated starch hydrolysates and mixtures thereof.

[0144] Water-soluble sweeteners derived from naturally occurringwater-soluble sweeteners include, but are not limited to, chlorinatedderivatives of sucrose, known, for example, under the productdesignation of Sucralose, and protein-based sweeteners such asthaumaoccous danielli (Thaumatin I and II).

[0145] Sorbitol solution supplies sweetness and body to the compositionand gives a desirable mouth feel. Sorbitol solution also enhancesflavor, prevents harsh taste and provides a fresh and lively sensationin the mouth. It also adds body and serves as a humectant.

[0146] In general, an effective amount of sweetener is utilized toprovide the level of sweetness desired in any particular embodiment ofthe oral compositions according to the present invention. This amountwill vary with the sweetener selected and the final form of the oralcomposition. The amount of sweetener normally present is from about0.0025% by weight to about 60% by weight of the oral composition. Theexact range of amounts for each type of sweetener in an oral compositionis readily determined by those skilled in the art.

[0147] The flavors that may be used in the invention include natural andartificial flavors known in the art. Suitable flavors include, but arenot limited to, mints, such as peppermint, citrus flavors such as orangeand lemon, artificial vanilla, cinnamon, various fruit flavors, and thelike. Anethole (or anise camphor, p-propenyl anisole) is a flavorconstituent of anise and fennel oils that are used widely as flavoringagent and antiseptic and was found useful in masking the harsh taste ofthymol.

[0148] The amount of flavor is normally a matter of preference subjectto the type of final oral composition, the individual flavor employedand the strength of flavor desired. The flavors are preferably utilizedin amounts that may range of from about 0.01% to about 6% by weight ofthe oral composition.

[0149] Coloring agents are used in amounts effective to produce an oralcomposition of the desired color. These coloring agents may beincorporated in amounts up to about 3% by weight of the oralcomposition. The coloring agents may also include natural food colorsand dyes suitable for food, drug and cosmetic applications. Thesecoloring agents are known as FD & C dyes and lakes. The coloringmaterials are preferably water-soluble. Illustrative nonlimitingexamples include the indigoid dye known as FD & C Blue No. 1, and D & CYellow No. 10. A full recitation of all FD & C colorants and theircorresponding chemical structures may be found in the Kirk-OthmerEncyclopedia of Chemical Technology, 3rd Edition, in volume 5 at pages857-884. A preferred opacifier, titanium dioxide, may be incorporated inamounts up to about 2.0% by weight, preferably less than about 1.0% byweight based on the total weight of the composition and most preferablyless than about 0.4% by weight.

[0150] Desensitizing agents used to diminish teeth sensitivity such asstrontium chloride, potassium nitrate and potassium citrate may also beincluded in the oral compositions of the present invention atconcentrations of from about 0.1 to 10% by weight.

[0151] Various other materials may be incorporated in the oralcompositions of the invention including whitening agents such as ureaperoxide and hydrogen peroxide, preservatives, such as sodium benzoate,chlorophyll compounds and/or ammoniated compounds such as urea,diammonium phosphate, and mixtures thereof. These adjuvants, whenpresent, are incorporated in the compositions in amounts which do notsubstantially adversely affect the desired properties.

[0152] The oral compositions of the present invention may be prepared bysuitably mixing the ingredients. By way of example, in the preparationof a mouthrinse, the antimicrobial agent of Formula (III) may bedispersed in a mixture containing for example, alcohol, humectant,surface-active agent, and salts such as sodium fluoride and potassiumphosphate, and a flavoring is then added and the resulting combinationmixed thoroughly. Dentifrices are prepared in a similar manner with theaddition, typically, of a thickener and a polishing agent.

[0153] The oral compositions of the present invention may beincorporated into dispersible oral films, oral film forming dentifrices,lozenges, or in chewing gum or other products, e.g. by stirring into awarm gum base or coating the outer surface of a gum base, illustrativeof which may be mentioned jelutone, rubber latex, vinylite resins, andthe like, desirably with conventional plasticizers or softeners, sugaror other sweeteners or carbohydrates such as glucose, sorbitol and thelike.

[0154] Oral film forming dentifrices include materials that may beapplied to dental and/or oral surfaces in a manner to form a film orcoating for reducing physical access to such surfaces by microorganisms,acid, food residues, debris, and the like, and for preventing growth ofharmful microorganisms. The resulting oral film thus provides aprotective physical barrier and enhances delivery of antimicrobialagents for minimizing attachment, propagation, growth or colonization ofbacteria on the dental surfaces. Such compositions may be water-soluble.Suitable oral film forming substances include silicone compounds,aminoalkyl silicones, organopolysiloxanes, dimethyl polysiloxanes,alkyl-dimethicone copolyols, alkoxy-dimethicone copolyols, cyclicsiloxane polymers and like substances.

[0155] The vehicle or carrier for a tablet or lozenge is desirably anon-cariogenic solid water-soluble polyhydric alcohol (polyol) such asmannitol, xylitol, sorbitol, malitol, a hydrogenated starch hydrolysate,Lycasin, hydrogenated glucose, hydrogenated disaccharides orhydrogenated polysaccharides, in an amount of from about 90 to 98% byweight. Solid salts such as sodium bicarbonate, sodium chloride,potassium bicarbonate or potassium chloride may totally or partiallyreplace the polyol carrier.

[0156] Tableting lubricants, in minor amounts of from about 0.1 to 5% byweight, may be incorporated into the tablet or lozenge formulation tofacilitate the preparation of both the tablets and lozenges. Suitablelubricants include vegetable oils such as coconut oil, magnesiumstearate, aluminum stearate, talc, starch and Carbowax.

[0157] Lozenge formulations contain about 2% gum as a barrier agent toprovide a shiny surface as opposed to a tablet which has a smoothfinish. Suitable non-cariogenic gums include kappa carrageenan,carboxymethyl cellulose, hydroxyethyl cellulose, and the like.

[0158] The lozenge or tablet may optionally be coated with a coatingmaterial such as waxes, shellac, carboxymethyl cellulose,polyethylene/maleic anhydride copolymer or kappa-carrageenan to furtherincrease the time it takes the tablet or lozenge to dissolve in themouth. The uncoated tablet or lozenge is slow dissolving, providing asustained release rate of active ingredients of about 3 to 5 minutes.Accordingly, the solid dose tablet and lozenge composition of thisinvention affords a relatively longer time period of contact of theteeth in the oral cavity with the active ingredients.

[0159] Dispersible oral film formulations contain an antimicrobialcompound of Formula (III) in a carrier comprising one or morewater-soluble polymers in combination with certain ingredients andprovides a therapeutic and/or cosmetic effect. The film is coated anddried utilizing existing coating technology and exhibits instantwettability followed by rapid dissolution/disintegration uponadministration in the oral cavity.

[0160] The foregoing discussion discloses and describes merely exemplaryembodiments of the present invention. One skilled in the art willreadily recognize from such discussion that various changes,modifications and variations can be made therein without departing fromthe spirit and scope of the invention as defined in the followingclaims.

EXAMPLE 1 Mouthrinse Formulation Containing Antimicrobial Compounds ofFormula (III)

[0161] A mouthrinse composition containing the ingredients and theamounts shown in Table 1 is prepared by mixing the alcohol solubleingredients 2 and 3 with ethanol. Water is added to the mixture. Watersoluble ingredients 4 through 9 are then added and blended thoroughly tothe mixture. About 1000 ml of water are added to the mixture to adjustthe final volume to yield the mouthrinse composition. TABLE 1Ingredients % by weight 1) Alcohol, USP 15 2) Antimicrobial Agents ofFormula (III) 0.05 3) Flavoring oil 0.1 4) Glycerine 3 5) Sodium laurylmethyl cocoyl taurate 0.3 6) Sodium citrate 0.08 7) Citric acid 0.02 8)Saccharin sodium 0.1 9) FD&C Green #3 0.0002 10) Water, USP QS to 100

EXAMPLE 2 Dentifrice Composition Containing Antimicrobial Compounds ofFormula (III)

[0162] A dentifrice composition containing the ingredients and theamounts shown in Table 2 is prepared by combining water, a portion ofthe humectant, the sweetener, the fluoride, and the water solublebuffers together. The remainder of the humectant is separately combinedwith the gum and then added to the initial mixture. Titanium oxide andsilicas are blended and then added to the mixture. The colorant, flavoroil, antimicrobial compounds of Formula (III) and the surfactant areadded and blended with the mixture. Table 2 TABLE 2 Ingredients % byweight 1) Glycerine 6 2) Sodium carboxymethylcellulose 1.2 3) Sorbitol40 4) Sodium monofluoriphosphate, USP 0.76 5) Saccharin sodium 1 6)Sodium phosphate, dibasic 0.03 7) Sodium phosphate, monobasic 0.25 8)Silicon dioxide, hydrated 15 9) Titanium dioxide 0.2 10) Flavor oil 211) Antimicrobial Agents of Formula (III) 0.5 12) FD&C Green #3 0.000213) Water, deionized QS to 100

EXAMPLE 3 Deodorant Composition Containing Antimicrobial Compounds ofFormula (II)

[0163] A deodorant composition containing the ingredients and theamounts shown in Table 3 is prepared by mixing together the polarsolvent, volatile nonpolar solvent, and the antimicrobial compounds ofFormula (II). Gellants are added to the resulting mixture and agitated.The mixture is heated to a temperature in the range from about 75 E to100E C. until the gellants melted and formed a substantially clear andtranslucent liquid. The resulting liquid mixture is slightly cooledprior to adding the fragrance. The resulting liquid mixture is pouredinto a suitable container and cooled to yield a solid form composition.TABLE 3 Ingredients % by weight 1) Propylene glycol 30 2) Glycerine 2.53) Butyl stearate 20 4) Antimicrobial Agents of Formula (II) 0.5 5)Propylene glycol monostearate 15 6) Water 32

EXAMPLE 4 Antibacterial Soap Composition Containing AntimicrobialCompounds of Formula (II)

[0164] An antibacterial soap composition containing the ingredients andthe amounts shown in Table 4 is prepared by agitating and mixing theingredients for thorough blending. TABLE 4 Ingredients % by weight 1)Sodium lauryl sulfate 67 2) Cocamidopropyl betaine 15 3) Glycerine 1 4)Propylene glycol 1 5) Antimicrobial Agents of Formula (II) 1 6)Fragrance 0.2 7) Water QS to 100

EXAMPLE 5 Antibacterial Cream or Ointment Composition ContainingAntimicrobial Compounds of Formula (II)

[0165] An antibacterial cream or ointment composition containing theingredients and amounts shown in Table 5 is prepared by dissolving theantimicrobial compound of Formula (II) into the solvent and surfactantingredients. The hydrophobic ingredients are then added to the resultingmixture and blended. The resulting mixture yields an emulsion having auniform creamy consistency. TABLE 5 Ingredients % by weight 1) Glycerine6 2) Propylene glycol 5.5 3) Sodium lauryl sulfate 1 4) Cetyl alcohol4.5 5) Cetyl palmitate 4 6) Steric alcohol 4.5 7) Steric acid 4 8) Whitepetrolatum 5 9) Antimicrobial Agents of Formula (II) 1 10) Water,deionized 64.5

What is claimed is:
 1. An antimicrobial composition comprising aneffective amount of at least one antimicrobial agent having the Formula:

wherein one of R₁ and R₂ is hydroxyl, and the other of R₁ and R₂, andeach of R₃, R₄, and R₅ are independently selected from the groupconsisting of hydrogen; hydroxyl; an alkyl group optionally substitutedwith hydroxyl; an alkenyl group; a cycloalkenyl group; an alkyl groupsubstituted with phenyl in which the phenyl may be substituted with amember selected from the group consisting of an alkyl group optionallysubstituted with hydroxyl and a cycloalkyl group optionally substitutedwith hydroxyl; a cycloalkyl group optionally substituted with hydroxyl;phenyl; phenyl substituted with a member selected from the groupconsisting of an alkyl group optionally substituted with hydroxyl, acycloalkyl group optionally substituted with hydroxyl, and an alkoxygroup; and,

wherein R_(x) is a member selected from the group consisting of an alkylgroup, benzyl, and phenyl; and each of R₆ and R₇ are selected from thegroup consisting of straight chain or branched alkyl optionallysubstituted with hydroxyl, and benzyl or phenyl optionally substitutedwith hydroxyl, alkyl, or alkoxy groups; with the proviso that: when R₁is hydroxyl, then R₂, R₃, R₄, and R₅ are not all hydrogen; when R₂ ishydroxyl, then R₁, R₃, R₄, and R₅ are not all hydrogen; when R₁ ishydroxyl, and each of R₃ and R₅ is hydrogen, then R₂ and R₄ are notindependently selected from methyl and hydrogen; when R₂ is hydroxyl,and each of R₁, R₃, R₄ is hydrogen, then R₅ is not methyl; when R₁ ishydroxyl, and each of R₃, R₄ and R₅ is hydrogen, then R₂ is notisobutyl; and when R₂ is hydroxyl and each of R₃, R₄, and R₅ ishydrogen, then R₁ is not selected from the group consisting of isopropyland isobutyl; and an antimicrobial effective carrier.
 2. Theantimicrobial composition of claim 1 wherein the antimicrobial effectivecarrier is selected from the group consisting of water, saline, alcohol,glycerine, propylene glycol, mineral oil, petrolatum, and mixturesthereof.
 3. The antimicrobial composition of claim 1 wherein thecompound has the formula (IIa) wherein each of R₃, R₄, and R₅ ishydrogen.
 4. The antimicrobial composition of claim 3 wherein R₁ ishydroxyl.
 5. The antimicrobial composition of claim 4 wherein R₂ is analkyl group.
 6. The antimicrobial composition of claim 5 wherein R₂ istert-butyl.
 7. The antimicrobial composition of claim 3 wherein R₂ ishydroxyl.
 8. The antimicrobial composition of claim 7 wherein R₁ isselected from the group consisting of an alkyl group optionallysubstituted with hydroxyl, a cycloalkyl group optionally substitutedwith hydroxyl, a phenyl group optionally substituted with hydroxyl, andbenzyl.
 9. The antimicrobial composition of claim 8 wherein R₁ isselected from the group consisting of isopropyl, butyl, tert-butyl,hexyl, cyclohexyl, phenyl and benzyl.
 10. The antimicrobial compositionof claim 1 wherein the compound has the formula (IIa) wherein R₁ ishydroxyl, and R₃ and R₅ are each hydrogen.
 11. The antimicrobialcomposition of claim 10 wherein R₂ is hydrogen and R₄ is an alkyl groupoptionally substituted with phenyl.
 12. The antimicrobial composition ofclaim 11 wherein R₄ is selected from the group consisting of tert-butyland benzyl.
 13. The antimicrobial composition of claim 10 wherein eachof R₂ and R₄ is tert-butyl.
 14. The antimicrobial composition of claim 1wherein the compound has the formula (IIa) wherein each of R₁, R₄, andR₅ is hydrogen, and R₃ is selected from the group consisting of an alkylgroup and an alkenyl group.
 15. The antimicrobial composition of claim14 wherein R₃ is isopropyl.
 16. The antimicrobial composition of claim 8wherein R₁ is selected from the group consisting of 2-hydroxycyclohexyl,3-hydroxycyclohexyl, 4-hydroxycyclohexyl, 2-hydroxycyclopentyl,3-hydroxycyclopentyl, 4-hydroxycyclopentyl, 2-hydroxycyclophenyl,3-hydroxycyclophenyl, and 4-hydroxycyclophenyl
 17. The antimicrobialcomposition of claim 4 wherein R₂ is selected from the group consistingof 2-hydroxyphenyl and 3-hydroxyphenyl.
 18. The antimicrobialcomposition of claim 1 wherein the compound has the formula (IIa)wherein R₂ is hydroxyl, each of R₁ and R₄ is hydrogen, R₃ is an alkylgroup, and R₅ is selected from the group consisting of an alkyl group,an alkyl group substituted with phenyl, a cycloalkenyl group, and abenzyl group optionally substituted with an alkyl group.
 19. Theantimicrobial composition of claim 18 wherein R₃ is isopropyl and R₅ isselected from the group consisting of 1-methyl-butyl, 1-phenyl-ethyl,cyclohex-2-enyl, 1-ethyl-1-methyl-propyl, and 3-methyl-benzyl.
 20. Theantimicrobial composition of claim 1 wherein the compound has theformula (IIa) wherein R₂ is hydroxyl, each of R₃ and R₄ is hydrogen, R₁is an alkyl group, and R₅ is selected from the group consisting of analkyl group and a benzyl group optionally substituted with an alkylgroup.
 21. The antimicrobial composition of claim 20 wherein R₁ isisopropyl, and R₅ is selected from the group consisting of1-ethyl-1-methyl-propyl, 3-methyl-benzyl, and tert-butyl.
 22. Theantimicrobial composition of claim 1 wherein the antimicrobial agent isselected from the group consisting of3-isopropyl-6-(1-methyl-butyl)-naphthalen-2-ol,3-isopropyl-6-(1-phenyl-ethyl)-naphthalen-2-ol,1-(4-hydroxynaphthyl)octan-1-one,6-(1-ethyl-1-methyl-propyl)-1-isopropyl-naphthalen-2-ol,6-(tert-butyl)-1-isoproyl-naphthalen-2-ol,6-(3-cyclohexenyl)-2-naphthol, 1-(6-hydroxy-2-naphthyl)hexan-1-one,1-isopropyl-6-(3-methyl-benzyl)-naphthalen-2-ol,1-(4-hydroxynaphthyl)hexan-1-one,6-cyclohex-2-enyl-3-isopropyl-naphthalen-2-ol, 6-cyclopentyl-2-naphthol,6-(1-ethyl-1-methyl-propyl)-3-isopropyl-naphthalen-2-ol,3-isopropyl-6-(3-methyl-benzyl)naphthalen-2-ol,6-(tert-butyl)-1-isopropyl-naphthalen-2-ol,6-(3-methyl-benzyl)-2-naphthol, 4-(2-hydroxycyclohexyl)-1-naphthol,4-(3-hydroxycyclohexyl)-1-naphthol, 1-(2-hydroxycyclohexyl)-2-naphthol,1-(3-hydroxycyclohexyl)-2-naphthol, 1-(4-hydroxycyclohexyl)-2-naphthol,1-cyclopentyl-2-naphthol, 1-(2-hydroxycyclopentyl)-2-naphthol,1-(3-hydroxycyclopentyl)-2-naphthol,4-(2-hydroxycyclopentyl)-1-naphthol, and4-(3-hydroxycyclopentyl)-1-naphthol.
 23. The antimicrobial compositionof claim 1 wherein the antimicrobial effective amount is from about0.0001% to 10.0% by weight based on the total weight of theantimicrobial composition.
 24. The antimicrobial composition of claim 23wherein the antimicrobial effective amount is from about 0.001% to 5.0%by weight.
 25. An oral composition comprising an antimicrobial effectiveamount of at least one antimicrobial agent having the Formula

wherein one of R₁ and R₂ is hydroxyl, and the other of R₁ and R₂, andeach of R₃, R₄, and R₅ are independently selected from the groupconsisting of hydrogen; hydroxyl; an alkyl group optionally substitutedwith hydroxyl; an alkenyl group; a cycloalkenyl group; an alkyl groupsubstituted with phenyl in which the phenyl may be substituted with amember selected from the group consisting of an alkyl group optionallysubstituted with hydroxyl and a cycloalkyl group optionally substitutedwith hydroxyl; a cycloalkyl group optionally substituted with hydroxyl;phenyl; phenyl substituted with a member selected from the groupconsisting of an alkyl group optionally substituted with hydroxyl, acycloalkyl group optionally substituted with hydroxyl, and an alkoxygroup; and,

wherein R_(x) is a member selected from the group consisting of an alkylgroup, benzyl, and phenyl; and each of R₆ and R₇ are selected from thegroup consisting of straight chain or branched alkyl optionallysubstituted with hydroxyl, and benzyl or phenyl optionally substitutedwith hydroxyl, alkyl, or alkoxy groups; with the proviso that: when R₁is hydroxyl, then R₂, R₃, R₄, and R₅ are not all hydrogen; when R₂ ishydroxyl, then R₁, R₃, R₄, and R₅ are not all hydrogen; and an orallyacceptable carrier.
 26. The oral composition of claim 25, wherein theorally acceptable carrier is selected from the group consisting ofwater, saline, alcohol, glycerine, propylene glycol, and mixturesthereof.
 27. The oral composition of claim 25 wherein the compound hasthe formula (IIIa) wherein each of R₃, R₄, and R₅ is hydrogen.
 28. Theoral composition of claim 27 wherein R₁ is hydroxyl.
 29. The oralcomposition of claim 28 wherein R₂ is an alkyl group.
 30. The oralcomposition of claim 29 wherein R₂ is tert-butyl.
 31. The oralcomposition of claim 27 wherein R₂ is hydroxyl.
 32. The oral compositionof claim 31 wherein R₁ is selected from the group consisting of an alkylgroup, a cycloalkyl group optionally substituted with hydroxyl, phenyloptionally substituted with hydroxyl, and benzyl.
 33. The oralcomposition of claim 32 wherein R₁ is selected from the group consistingof isopropyl, butyl, tert-butyl, hexyl, cyclohexyl, phenyl and benzyl.34. The oral composition of claim 25 wherein the compound has theformula (IIIa) wherein R₁ is hydroxyl, and R₃ and R₅ are each hydrogen.35. The oral composition of claim 34 wherein R₂ is hydrogen and R₄ is analkyl group optionally substituted with phenyl.
 36. The oral compositionof claim 35 wherein R₄ is selected from the group consisting oftert-butyl and benzyl.
 37. The oral composition of claim 34 wherein eachof R₂ and R₄ is tert-butyl.
 38. The oral composition of claim 25 whereinthe compound has the formula (IIIa) wherein each of R₁, R₄, and R₅ ishydrogen, R₂ is hydroxyl and R₃ is an alkyl group.
 39. The oralcomposition of claim 38 wherein R₃ is isopropyl.
 40. The oralcomposition of claim 32 wherein R₁ is selected from the group consistingof 2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl,2-hydroxycyclopentyl, 3-hydroxycyclopentyl, cyclopentyl,2-hydroxyphenyl, 3-hydroxyphenyl, and 4-hydroxyphenyl.
 41. An oralcomposition of claim 25 wherein the compound has the formula (IIIa)wherein R₁ is hydroxyl, each of R₃, R₄, and R₅ is hydrogen, and R₂ isselected from the group consisting of 2-hydroxyphenyl and3-hydroxyphenyl.
 42. The oral composition of claim 25 wherein thecompound has the formula (IIIa) wherein R₂ is hydroxyl, each of R₁ andR₄ is hydrogen, R₃ is an alkyl group, and R₅ is selected from the groupconsisting of an alkyl group, an alkyl group substituted with phenyl, acycloalkenyl group, and benzyl substituted with an alkyl group.
 43. Theoral composition of claim 42 wherein R₃ is isopropyl and R₅ is selectedfrom the group consisting of 1-methyl-butyl, 1-phenyl-ethyl,cyclohex-2-enyl, 1-ethyl-1-methyl-propyl, and 3-methyl-benzyl.
 44. Theoral composition of claim 25 wherein the compound has the formula (IIIa)wherein R₂ is hydroxyl, each of R₃ and R₄ is hydrogen, R₁ is an alkylgroup, and R₅ is selected from the group consisting of an alkyl groupand benzyl substituted with an alkyl group.
 45. The oral composition ofclaim 44 wherein R₁ is isopropyl, and R₅ is selected from the groupconsisting of 1-ethyl-1-methyl-propyl, 3-methyl-benzyl, and tert-butyl.46. The oral composition of claim 25 wherein the antimicrobial agent isselected from the group consisting of3-isopropyl-6-(1-methyl-butyl)-naphthalen-2-ol,3-isopropyl-6-(1-phenyl-ethyl)-naphthalen-2-ol,1-(4-hydroxynaphthyl)octan-1-one,6-(1-ethyl-1-methyl-propyl)-1-isopropyl-naphthalen-2-ol,6-(tert-butyl)-1-isoproyl-naphthalen-2-ol,6-(3-cyclohexenyl)-2-naphthol, 1-(6-hydroxy-2-naphthyl)hexan-1-one,1-isopropyl-6-(3-methyl-benzyl)-naphthalen-2-ol,1-(4-hydroxynaphthyl)hexan-1-one,6-cyclohex-2-enyl-3-isopropyl-naphthalen-2-ol, 6-cyclopentyl-2-naphthol,6-(1-ethyl-1-methyl-propyl)-3-isopropyl-naphthalen-2-ol,3-isopropyl-6-(3-methyl-benzyl)naphthalen-2-ol,6-(tert-butyl)-1-isopropyl-naphthalen-2-ol,6-(3-methyl-benzyl)-2-naphthol, 4-(2-hydroxycyclohexyl)-1-naphthol,4-(3-hydroxycyclohexyl)-1-naphthol, 1-(2-hydroxycyclohexyl)-2-naphthol,1-(3-hydroxycyclohexyl)-2-naphthol, 1-(4-hydroxycyclohexyl)-2-naphthol,1-cyclopentyl-2-naphthol, 1-(2-hydroxycyclopentyl)-2-naphthol,1-(3-hydroxycyclopentyl)-2-naphthol,4-(2-hydroxycyclopentyl)-1-naphthol, and4-(3-hydroxycyclopentyl)-1-naphthol.
 47. The oral composition of claim25 wherein the antimicrobial effective amount is from about 0.0001% to10.0% by weight based on the total weight of the antimicrobialcomposition.
 48. The oral composition of claim 47 wherein theantimicrobial effective amount is from about 0.001% to 5.0% by weight.49. The oral composition of claim 25 further comprising at least oneessential oil wherein at least one essential oil is selected from thegroup consisting of thymol, menthol, eucalyptol, methyl salicylate, andcombinations thereof.
 50. The oral composition of claim 49 wherein theessential oils comprise: an amount of from about 0.005 to 0.5% menthol;an amount of from about 0.005 to 0.5% eucalyptol; an amount of fromabout 0.005 to 0.5% methyl salicylate; and an amount of from about 0.005to 0.5% thymol.
 51. The oral composition of claim 25 further comprisingan antimicrobial enhancing agent in an amount of from about 0.05% to 5%by weight.
 52. The oral composition of claim 51 wherein theantimicrobial enhancing agent includes an average molecular weight offrom about 100 to about 5,000,000.
 53. The oral composition of claim 51wherein the antimicrobial enhancing agent is an anionic polymercontaining one or more delivery-enhancing groups and retention-enhancinggroups.
 54. The oral composition of claim 53 wherein the antimicrobialenhancing agent is an anionic polycarboxylate.
 55. A method of reducingthe presence of microorganisms on a substrate comprising treating thesubstrate with an antimicrobial effective amount of the antimicrobialcomposition of claim
 1. 56. The method of claim 55 wherein theantimicrobial effective carrier is selected from the group consisting ofwater, saline, alcohol, glycerine, propylene glycol, mineral oil,petrolatum, and mixtures thereof.
 57. A method of reducing the presenceof microorganisms in an oral cavity comprising administering into theoral cavity an antimicrobial effective amount of the oral composition ofclaim
 25. 58. The method of claim 57 wherein the antimicrobial effectiveamount is from about 0.0001 to 10% by weight.
 59. The method of claim 58wherein the antimicrobial effective amount is from about 0.001 to 5% byweight.
 60. The method of claim 59 wherein the oral composition is inthe form of a member selected from the group consisting of a mouthrinse,a dentifrice, a chewing gum, a lozenge, a dispersible oral film, and anoral film forming dentifrice.
 61. Compounds of Formula

wherein one of R₁ and R₂ is hydroxyl, and the other of R₁ and R₂ isselected from the group consisting of hydrogen, an alkyl groupoptionally substituted with hydroxyl, a cycloalkyl group optionallysubstituted with hydroxyl, and an hydroxyphenyl group; R₃ is selectedfrom the group consisting of hydrogen and an alkyl group optionallysubstituted with hydroxyl; R₄ is selected from the group consisting ofhydrogen, a C₂ to C₆ straight chain or branched alkyl group optionallysubstituted with hydroxyl, a hydroxycycloalkyl group, and,

wherein R_(x) is an alkyl group; R₅ is selected from hydrogen, an alkylgroup optionally substituted with hydroxyl, a cycloalkyl group, acycloalkenyl group, an alkyl group substituted with phenyl, benzylsubstituted with an alkyl group, and

wherein R_(x) is an alkyl group; each of R₆ and R₇ are selected from thegroup consisting of straight chain or branched alkyl optionallysubstituted with hydroxyl, and benzyl or phenyl optionally substitutedwith hydroxyl, alkyl, or alkoxy groups; with the proviso that: when R₁is hydroxyl, then R₂, R₃, R₄, and R₅ are not all hydrogen; when R₂ ishydroxyl, then R₁, R₃, R₄, and R₅ are not all hydrogen; when R₂ ishydroxyl, then R₅ is not methyl; when R₂ is hydroxyl and each of R₃, R₄,and R₅ is hydrogen, then R₁ is not selected from the group consisting ofisopropyl and isobutyl; when R₁ is hydroxyl and each of R₃, R₄ and R₅ ishydrogen, then R₂ is not 4-hydroxyphenyl; and when R₁ is hydroxyl andeach of R₃, and R₅ is hydrogen, then R₂ and R₄ are not both tert-butyl;with the further proviso that R₆ and R₇ are not both tert-butyl.
 62. Thecompound of claim 61 wherein the compound has the formula (Ia) whereinR₁ is hydroxyl, each of R₂, R₃, and R₄ is hydrogen, and R₅ is selectedfrom the group consisting of a hydroxycycloalkyl group and,

wherein R_(x) is an alkyl group.
 63. The compound of claim 62 wherein R₅is selected from the group consisting of 2-hydroxycyclohexyl,3-hydroxycyclohexyl, 4-hydroxycyclohexyl, 2-hydroxycyclopentyl,3-hydroxycyclopentyl, and,

wherein R_(x) is selected from the group consistng of n-heptyl andn-pentyl.
 64. The compound of claim 61 wherein the compound has theformula (Ia) wherein R₂ is hydroxyl, each of R₃, R₄, and R₅ is hydrogen,and R₁ is selected from the group consisting of a cycloalkyl groupoptionally substituted with hydroxyl and an hydroxyphenyl group.
 65. Thecompound of claim 64 wherein R₁ is selected from the group consisting of2-hydroxycyclohexyl, 3-hydroxycyclohexyl, 4-hydroxycyclohexyl,2-hydroxycyclopentyl, 3-hydroxycyclopentyl, cyclopentyl,2-hydroxyphenyl, 3-hydroxyphenyl, and 4-hydroxyphenyl.
 66. The compoundof claim 61 wherein the compound has the formula (Ia) wherein R₂ ishydroxyl, each of R₁ and R₄ is hydrogen, R₃ is an alkyl group, and R₅ isselected from the group consisting of an alkyl group, an alkyl groupsubstituted with phenyl, a cycloalkenyl group, and benzyl substitutedwith an alkyl group.
 67. The compound of claim 66 wherein R₃ isisopropyl and R₅ is selected from the group consisting of1-methyl-butyl, 1-phenyl-ethyl, cyclohex-2-enyl,1-ethyl-1-methyl-propyl, and 3-methyl-benzyl.
 68. The compound of claim61 wherein the compound has the formula (Ia) wherein R₂ is hydroxyl,each of R₃ and R₄ is hydrogen, R₁ is an alkyl group, and R₅ is selectedfrom the group consisting of an alkyl group and benzyl substituted withan alkyl group.
 69. The compound of claim 68 wherein R₁ is isopropyl,and R₅ is selected from the group consisting of 1-ethyl-1-methyl-propyl,3-methyl-benzyl, and tert-butyl.
 70. The compound of claim 61 whereinthe compound has the formula (Ia) wherein R₂ is hydroxyl, each of R₁,R₃, and R₄ is hydrogen, and R₅ is selected from the group consisting ofa cycloalkenyl group, a cycloalkyl group, benzyl substituted with analkyl group, and,

wherein R_(x) is an alkyl group.
 71. The compound of claim 70 wherein R₅is selected from the group consisting of 3-cyclohex-2-enyl, cyclopentyl,3-methyl-benzyl, and,

wherein R_(x) is n-pentyl.
 72. A compound of claim 60 wherein thecompound has the formula (Ia) wherein R₁ is hydroxyl, each of R₃, R₄,and R₅ is hydrogen, and R₂ is selected from the group consisting of2-hydroxyphenyl and 3-hydroxyphenyl.
 73. An antimicrobial composition_ofclaim 1 wherein the antimicrobial agent has the formula (IIb) wherein R₁is hydroxyl and R₆ and R₇ are each independently selected from the groupconsisting of isopropyl, tert-butyl, phenyl and benzyl.
 74. A oralcomposition of claim 25 wherein the antimicrobial agent has the formula(IIIb) wherein R₁ is hydroxyl and R₆ and R₇ are each independentlyselected from the group consisting of isopropyl, tert-butyl, phenyl andbenzyl.
 75. A compound of claim 60 wherein the compound has the formula(Ib) wherein R₁ is hydroxyl and R₆ and R₇ are each independentlyselected from the group consisting of isopropyl, tert-butyl, phenyl andbenzyl.